Case Reports Reveal Individualized Risk Patterns in Triple-Negative Breast Cancer Treatment
Key Insights
A review of 24 published TNBC case reports (2020–2025) found that 41.7% documented serious treatment-related toxicity, including two fatal events.
Patient-specific vulnerabilities such as BRCA1/2 (search) alterations, viral carriage, and rare DNA-repair syndromes significantly influenced therapeutic risk and outcomes.
Biomarker-guided therapy was reported in 45.8% of cases, with objective response or disease stabilization described in nine of those eleven cases.
A descriptive synthesis of 24 published case reports on triple-negative breast cancer (search) (TNBC) therapy, spanning 2020 to 2025, highlights how patient-specific vulnerabilities, tumor heterogeneity, and biomarker-guided treatment selection shape clinical outcomes and treatment-related complications. The review, published in Therapeutics and Clinical Risk Management, underscores that TNBC management extends beyond receptor status alone, requiring individualized risk assessment and multidisciplinary care.
The included cases comprised female patients with a median age of 45 years (range, 28–87). Metastatic or advanced disease was described in 45.8% of reports, while 41.7% involved early or localized disease. The remaining cases covered local recurrence or unclear disease settings.
Biomarker Landscape and Treatment Selection
Molecular profiling revealed substantial heterogeneity across the case reports. BRCA1/2 (search) alterations and PD-L1 (search) status were each reported in five cases (20.8%), while PIK3CA alterations and circulating tumor DNA or disseminated tumor cell findings appeared in two cases each (8.3%). BRAF alteration and NTRK fusion were each documented in a single case. Overall, 12 cases (50.0%) harbored an actionable or resistance-informative biomarker signal, and biomarker-matched therapy was administered in 11 cases (45.8%). Among these 11, the source reports described objective response or at least transient disease stabilization in nine cases.
Immunotherapy was reported in nine of 24 cases (37.5%), with pembrolizumab being the most frequently cited immune checkpoint inhibitor (five cases), followed by atezolizumab (three cases) and camrelizumab (two cases). Tumor-infiltrating lymphocyte therapy combined with interleukin-2 was reported once in a highly refractory setting.
Clinical Outcomes and Toxicity Patterns
Within the selected case-report dataset, 17 cases (70.8%) were categorized as favorable outcomes, four cases (16.7%) as death or failure, and three cases (12.5%) as ongoing or unclear. Complete or near-complete disease eradication—including complete response, pathological complete response, no evidence of disease, or near-pCR—was described in 14 cases (58.3%).
Serious toxicity or clinically significant complications were documented in 10 cases (41.7%), including two fatal treatment-related events (8.3%). Reported complications included hepatitis B virus reactivation with severe transaminitis, immune-related Sjögren syndrome, hepatic sarcoidosis-like reaction mimicking metastatic disease, posterior reversible encephalopathy syndrome, hyperprogressive disease after immune checkpoint inhibition, grade 4 myelosuppression, treatment intolerance, therapy-related myelodysplastic syndrome, and fatal inflammatory toxicity after adoptive cell therapy with interleukin-2.
Host Vulnerabilities and Individualized Risk
Several cases illustrated how baseline host factors influence therapeutic risk. Gürbüz et al. (2024) reported that Bloom syndrome heightened vulnerability to DNA-damaging chemotherapy and radiotherapy, resulting in fatal therapy-related myelodysplastic syndrome and sepsis. Al-Bitar et al. (2025) described TNBC management complicated by hepatitis B virus reactivation and synchronous rectal adenocarcinoma, demonstrating how viral carriage and concurrent malignancies can impact the safety and sequencing of systemic therapy. Pregnancy-associated TNBC further underscored the necessity for individualized treatment timing and multidisciplinary decision-making.
Tumor Heterogeneity and Molecular Reassessment
The reviewed cases confirmed that TNBC encompasses distinct clinical and biological subtypes. While many patients presented with high-grade invasive ductal carcinoma, some exhibited rare or diagnostically challenging tumor types, including metaplastic breast carcinoma, inflammatory breast cancer, acinic cell carcinoma, pleomorphic lobular carcinoma, and secretory breast carcinoma. Martorana et al. (2023) demonstrated phenotypic plasticity with receptor conversion under selective pressure, supporting repeat biopsy and reassessment of receptor and molecular status when disease biology appears to change.
Study Limitations
The authors acknowledge several limitations. The analysis is based on published case reports, which are intrinsically subject to publication bias favoring exceptional responses, rare histologies, and severe toxicities. The reports were heterogeneous in disease stage, histology, biomarker testing, treatment regimen, and follow-up duration, precluding meta-analysis or comparative effectiveness assessment. Adverse-event grading was reported inconsistently, and treatment attribution was often uncertain due to multimodal or sequential therapy. The search strategy was limited to PubMed-indexed sources.
The review concludes that these case-derived signals support individualized risk assessment, early multidisciplinary consultation, and prospective evaluation of toxicity surveillance strategies in TNBC, while emphasizing that findings remain descriptive and hypothesis-generating rather than practice-changing.